Self-Referencing Nanopipette Sensor for the Single-Cell Determination of Carcinoembryonic Antigen (CEA) Using Electrochemical Ligands

Early detection of cancer biomarkers is essential for accurate diagnosis and timely therapeutic intervention. Carcinoembryonic antigen (CEA), a nonspecific and broad-spectrum tumor-associated biomarker, is extensively employed for the early screening and diagnosis of multiple malignancies. In recent years, electrochemical nanopipette sensing technology has been increasingly explored for clinical disease detection owing to its high sensitivity, low background interference, and inherent suitability for single-cell analysis. Nucleic acid aptamers, characterized by target-specific three-dimensional conformations, are capable of binding a wide range of molecular targets with high affinity and selectivity. In this work, a functional nanopipette microelectrode was rationally designed and fabricated by immobilizing nucleic acid aptamers onto electrochemical nanopipette electrodes, enabling label-free detection of CEA at the single-cell level. Under optimized conditions, the resulting sensor achieved a limit of detection as low as 1.27 pg/mL.